By studying the apparent volumes of distribution of high affinity and low affinity in rabbits, we were able to define a body space which corresponds to insulin receptors. This space has limited capacity since increasing concentrations of unlabeled insulin progressively decreased the distribution volume of the high affinity insulin. In addition, insulin binding in vivo is rapid and readily reversible. This reversibility shows that the receptor bound hormone is in rapid equilibrium with the plasma compartment and further suggests that the insulin receptor may function as a reservoir for the circulating hormone, analogous to the plasma binding proteins for steroid and thyroid hormones. The direct in vivo studies reflect the actual number of receptors exposed to hormone under physiological conditions. This is not a destructive technique. This is really applicable to study of other hormones where target cell is unavailable or unknown.